tbuckley/cabot-search huggingface dataset:
Sequencing directly from antigen-detection rapid diagnostic tests in Belgium, 2022: a gamechanger in genomic surveillance?
Authors: Annabel Rector, Mandy Bloemen, Gilberte Schiettekatte, Piet Maes, Marc Van Ranst, Elke Wollants
Journal: Eurosurveillance (2023)

Background Lateral flow antigen-detection rapid diagnostic tests (Ag-RDTs) for viral infections constitute a fast, cheap and reliable alternative to nucleic acid amplification tests (NAATs). Whereas leftover material from NAATs can be employed for genomic analysis of positive samples, there is a paucity of information on whether viral genetic characterisation can be achieved from archived Ag-RDTs. Aim To evaluate the possibility of retrieving leftover material of several viruses from a range of Ag-RDTs, for molecular genetic analysis. Methods Archived Ag-RDTs which had been stored for up to 3 months at room temperature were used to extract viral nucleic acids for subsequent RT-qPCR, Sanger sequencing and Nanopore whole genome sequencing. The effects of brands of Ag-RDT and of various ways to prepare Ag-RDT material were evaluated. Results SARS-CoV-2 nucleic acids were successfully extracted and sequenced from nine different brands of Ag-RDTs for SARS-CoV-2, and for five of these, after storage for 3 months at room temperature. The approach also worked for Ag-RDTs for influenza virus (n = 3 brands), as well as for rotavirus and adenovirus 40/41 (n = 1 brand). The buffer of the Ag-RDT had an important influence on viral RNA yield from the test strip and the efficiency of subsequent sequencing. Conclusion Our finding that the test strip in Ag-RDTs is suited to preserve viral genomic material, even for several months at room temperature, and therefore can serve as source material for genetic characterisation could help improve global coverage of genomic surveillance for SARS-CoV-2 as well as for other viruses.
Pathogenic antibody response to glucose-6-phosphate isomerase targets a modified epitope uniquely exposed on joint cartilage
Authors: Taotao Li, Changrong Ge, Alexander Krämer, Outi Sareila, Monica Leu Agelii, Linda Johansson, Kristina Forslind, Erik Lönnblom, Min Yang, Bingze Xu, Qixing Li, Lei Cheng, Göran Bergström, Gonzalo Fernandez, Alf Kastbom, Solbritt Rantapää-Dahlqvist, Inger Gjertsson, Rikard Holmdahl
Journal: Annals of the Rheumatic Diseases (2023)

Objectives To identify the arthritogenic B cell epitopes of glucose-6-phosphate isomerase (GPI) and their association with rheumatoid arthritis (RA). Methods IgG response towards a library of GPI peptides in patients with early RA, pre-symptomatic individuals and population controls, as well as in mice, were tested by bead-based multiplex immunoassays and ELISA. Monoclonal IgG were generated, and the binding specificity and affinity were determined by ELISA, gel size exclusion chromatography, surface plasma resonance and X-ray crystallography. Arthritogenicity was investigated by passive transfer experiments. Antigen-specific B cells were identified by peptide tetramer staining. Results Peptide GPI 293-307 was the dominant B cell epitope in K/BxN and GPI-immunised mice. We could detect B cells and low levels of IgM antibodies binding the GPI 293-307 epitopes, and high affinity anti-GPI 293-307 IgG antibodies already 7 days after GPI immunisation, immediately before arthritis onset. Transfer of anti-GPI 293-307 IgG antibodies induced arthritis in mice. Moreover, anti-GPI 293-307 IgG antibodies were more frequent in individuals prior to RA onset (19%) than in controls (7.5%). GPI 293-307 -specific antibodies were associated with radiographic joint damage. Crystal structures of the Fab–peptide complex revealed that this epitope is not exposed in native GPI but requires conformational change of the protein in inflamed joint for effective recognition by anti-GPI 293-307 antibodies. Conclusions We have identified the major pathogenic B cell epitope of the RA-associated autoantigen GPI, at position 293–307, exposed only on structurally modified GPI on the cartilage surface. B cells to this neo-epitope escape tolerance and could potentially play a role in the pathogenesis of RA.
Consumer Views on Privacy Protections and Sharing of Personal Digital Health Information
Authors: Ravi Gupta, Raghuram Iyengar, Meghana Sharma, Carolyn C. Cannuscio, Raina M. Merchant, David A. Asch, Nandita Mitra, David Grande
Journal: JAMA Network Open (2023)

Importance Digital health information has many potential health applications, but privacy is a growing concern among consumers and policy makers. Consent alone is increasingly seen as inadequate to safeguard privacy. Objective To determine whether different privacy protections are associated with consumers’ willingness to share their digital health information for research, marketing, or clinical uses. Design, Setting, and Participants This 2020 national survey with an embedded conjoint experiment recruited US adults from a nationally representative sample with oversampling of Black and Hispanic individuals. Willingness to share digital information across 192 different scenarios reflecting the product of 4 possible privacy protections, 3 uses of information, 2 users of information, and 2 sources of digital information was evaluated. Each participant was randomly assigned 9 scenarios. The survey was administrated between July 10 and July 31, 2020, in Spanish and English. Analysis for this study was conducted between May 2021 and July 2022. Main Outcomes and Measures Participants rated each conjoint profile on a 5-point Likert scale measuring their willingness to share their personal digital information (with 5 indicating the most willingness to share). Results are reported as adjusted mean differences. Results Of the 6284 potential participants, 3539 (56%) responded to the conjoint scenarios. A total of 1858 participants (53%) were female, 758 (21%) identified as Black, 833 (24%) identified as Hispanic, 1149 (33%) had an annual income less than $50 000, and 1274 (36%) were 60 years or older. Participants were more willing to share health information with the presence of each individual privacy protection, including consent (difference, 0.32; 95% CI, 0.29-0.35; P &amp;amp;lt; .001), followed by data deletion (difference, 0.16; 95% CI, 0.13-0.18; P &amp;amp;lt; .001), oversight (difference, 0.13; 95% CI, 0.10-0.15; P &amp;amp;lt; .001), and transparency of data collected (difference, 0.08; 95% CI, 0.05-0.10; P &amp;amp;lt; .001). The relative importance (importance weight on a 0%-100% scale) was greatest for the purpose of use (29.9%) but when considered collectively, the 4 privacy protections together were the most important (51.5%) factor in the conjoint experiment. When the 4 privacy protections were considered separately, consent was the most important (23.9%). Conclusions and Relevance In this survey study of a nationally representative sample of US adults, consumers’ willingness to share personal digital health information for health purposes was associated with the presence of specific privacy protections beyond consent alone. Additional protections, including data transparency, oversight, and data deletion may strengthen consumer confidence in sharing their personal digital health information.
CD39/CD73/A2AR pathway and cancer immunotherapy
Authors: Chenglai Xia, Shuanghong Yin, Kenneth K. W. To, Liwu Fu
Journal: Molecular Cancer (2023)

Abstract Cancer development is closely associated with immunosuppressive tumor microenvironment (TME) that attenuates antitumor immune responses and promotes tumor cell immunologic escape. The sequential conversion of extracellular ATP into adenosine by two important cell-surface ectonucleosidases CD39 and CD73 play critical roles in reshaping an immunosuppressive TME. The accumulated extracellular adenosine mediates its regulatory functions by binding to one of four adenosine receptors (A1R, A2AR, A2BR and A3R). The A2AR elicits its profound immunosuppressive function via regulating cAMP signaling. The increasing evidence suggests that CD39, CD73 and A2AR could be used as novel therapeutic targets for manipulating the antitumor immunity. In recent years, monoclonal antibodies or small molecule inhibitors targeting the CD39/CD73/A2AR pathway have been investigated in clinical trials as single agents or in combination with anti-PD-1/PD-L1 therapies. In this review, we provide an updated summary about the pathophysiological function of the adenosinergic pathway in cancer development, metastasis and drug resistance. The targeting of one or more components of the adenosinergic pathway for cancer therapy and circumvention of immunotherapy resistance are also discussed. Emerging biomarkers that may be used to guide the selection of CD39/CD73/A2AR-targeting treatment strategies for individual cancer patients is also deliberated.
A parathyroid hormone/salt-inducible kinase signaling axis controls renal vitamin D activation and organismal calcium homeostasis
Authors: Sung-Hee Yoon, Mark B. Meyer, Carlos Arevalo, Murat Tekguc, Chengcheng Zhang, Jialiang S. Wang, Christian D. Castro Andrade, Katelyn Strauss, Tadatoshi Sato, Nancy A. Benkusky, Seong Min Lee, Rebecca Berdeaux, Marc Foretz, Thomas B. Sundberg, Ramnik J. Xavier, Charles H. Adelmann, Daniel J. Brooks, Anthony Anselmo, Ruslan I. Sadreyev, Ivy A. Rosales, David E. Fisher, Navin Gupta, Ryuji Morizane, Anna Greka, J. Wesley Pike, Michael Mannstadt, Marc N. Wein
Journal: Journal of Clinical Investigation (2023)

The renal actions of parathyroid hormone (PTH) promote 1,25-vitamin D generation; however, the signaling mechanisms that control PTH-dependent vitamin D activation remain unknown. Here we demonstrated that Salt Inducible Kinases (SIKs) orchestrated renal 1,25-vitamin D production downstream of PTH signaling. PTH inhibited SIK cellular activity by cAMP-dependent PKA phosphorylation. Whole tissue and single cell transcriptomics demonstrated that both PTH and pharmacologic SIK inhibitors regulated a vitamin D gene module in the proximal tubule. SIK inhibitors increased 1,25-vitamin D production and renal Cyp27b1 mRNA expression in mice and in human embryonic stem cell-derived kidney organoids. Global- and kidney-specific Sik2/Sik3 mutant mice showed Cyp27b1 upregulation, elevated serum 1,25-vitamin D, and PTH-independent hypercalcemia. The SIK substrate CRTC2 showed PTH and SIK inhibitor-inducible binding to key Cyp27b1 regulatory enhancers in the kidney, which were also required for SIK inhibitors to increase Cyp27b1 in vivo. Lastly, in a podocyte injury model of chronic kidney disease-mineral bone disorder (CKD-MBD), SIK inhibitor treatment stimulated renal Cyp27b1 expression and 1,25-vitamin D production. Together, these results demonstrated a PTH/SIK/CRTC signaling axis in the kidney that controls Cyp27b1 expression and 1,25-vitamin D synthesis. These findings indicate that SIK inhibitors might be helpful to stimulate 1,25-vitamin D production in CKD-MBD.
Letter to the Editor: Knowledge gap in assessing the risk of a human pandemic via mammals’ infection with highly pathogenic avian influenza A(H5N1)
Authors: Hiroshi Nishiura, Taishi Kayano, Katsuma Hayashi, Tetsuro Kobayashi, Yuta Okada
Journal: Eurosurveillance (2023)

Preview this article: Letter to the Editor: Knowledge gap in assessing the risk of a human pandemic via mammals' infection with highly pathogenic avian influenza A(H5N1), Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/28/9/eurosurv-28-9-4-1.gif
Correction: Chromatin Rewiring by Mismatch Repair Protein MSH2 Alters Cell Adhesion Pathways and Sensitivity to BET Inhibition in Gastric Cancer
Authors: Amrita M. Nargund, Chang Xu, Amit Mandoli, Atsushi Okabe, Gao Bin Chen, Kie Kyon Huang, Taotao Sheng, Xiaosai Yao, Jia Ming Nickolas Teo, Raghav Sundar, Yee Jiun Kok, Yi Xiang See, Manjie Xing, Zhimei Li, Chern Han Yong, Aparna Anand, Zul Fazreen Bin Adam Isa, Lai Fong Poon, Michelle Shu Wen Ng, Javier Yu Peng Koh, Wen Fong Ooi, Su Ting Tay, Xuewen Ong, Angie Lay Keng Tan, Duane T. Smoot, Hassan Ashktorab, Heike I. Grabsch, Melissa J. Fullwood, Bin Tean Teh, Xuezhi Bi, Atsushi Kaneda, Shang Li, Patrick Tan
Journal: Cancer Research (2023)

In the original version of this article (1), Duane T. Smoot and Hassan Ashktorab are mistakenly omitted from the author list. This error has been corrected in the latest online HTML and PDF versions of the article and the author contributions and disclosures have been updated as necessary. The authors regret this error.
Reversal of Lactate and PD-1–mediated Macrophage Immunosuppression Controls Growth of PTEN/p53-deficient Prostate Cancer
Authors: Kiranj Chaudagar, Hanna M. Hieromnimon, Rimpi Khurana, Brian Labadie, Taghreed Hirz, Shenglin Mei, Raisa Hasan, Jordan Shafran, Anne Kelley, Eva Apostolov, Ghamdan Al-Eryani, Kate Harvey, Srikrishnan Rameshbabu, Mayme Loyd, Kaela Bynoe, Catherine Drovetsky, Ani Solanki, Erica Markiewicz, Marta Zamora, Xiaobing Fan, Stephan Schürer, Alex Swarbrick, David B. Sykes, Akash Patnaik
Journal: Clinical Cancer Research (2023)

Phosphatase and tensin homolog (PTEN) loss of function occurs in approximately 50% of patients with metastatic castrate-resistant prostate cancer (mCRPC), and is associated with poor prognosis and responsiveness to standard-of-care therapies and immune checkpoint inhibitors. While PTEN loss of function hyperactivates PI3K signaling, combinatorial PI3K/AKT pathway and androgen deprivation therapy (ADT) has demonstrated limited anticancer efficacy in clinical trials. Here, we aimed to elucidate mechanism(s) of resistance to ADT/PI3K-AKT axis blockade, and to develop rational combinatorial strategies to effectively treat this molecular subset of mCRPC.Prostate-specific PTEN/p53-deficient genetically engineered mice (GEM) with established 150-200 mm3 tumors, as assessed by ultrasound, were treated with either ADT (degarelix), PI3K inhibitor (copanlisib), or anti-PD-1 antibody (aPD-1), as single agents or their combinations, and tumors were monitored by MRI and harvested for immune, transcriptomic, and proteomic profiling, or ex vivo co-culture studies. Single-cell RNA sequencing on human mCRPC samples was performed using 10X Genomics platform.Coclinical trials in PTEN/p53-deficient GEM revealed that recruitment of PD-1-expressing tumor-associated macrophages (TAM) thwarts ADT/PI3Ki combination-induced tumor control. The addition of aPD-1 to ADT/PI3Ki combination led to TAM-dependent approximately 3-fold increase in anticancer responses. Mechanistically, decreased lactate production from PI3Ki-treated tumor cells suppressed histone lactylation within TAM, resulting in their anticancer phagocytic activation, which was augmented by ADT/aPD-1 treatment and abrogated by feedback activation of Wnt/β-catenin pathway. Single-cell RNA-sequencing analysis in mCRPC patient biopsy samples revealed a direct correlation between high glycolytic activity and TAM phagocytosis suppression.Immunometabolic strategies that reverse lactate and PD-1-mediated TAM immunosuppression, in combination with ADT, warrant further investigation in patients with PTEN-deficient mCRPC.
Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary
Authors: Alvar Agustí, Bartolome R. Celli, Gerard J. Criner, David Halpin, Antonio Anzueto, Peter Barnes, Jean Bourbeau, MeiLan K. Han, Fernando J. Martinez, Maria Montes de Oca, Kevin Mortimer, Alberto Papi, Ian Pavord, Nicolas Roche, Sundeep Salvi, Don D. Sin, Dave Singh, Robert Stockley, M. Victorina López Varela, Jadwiga A. Wedzicha, Claus F. Vogelmeier
Journal: European Respiratory Journal (2023)

<b>Executive summary of the Global Strategy for Prevention, Diagnosis and Management of COPD 2023: the latest evidence-based strategy document from the Global Initiative for Chronic Obstructive Lung Disease (GOLD</b><b>)</b> https://bit.ly/3KCaTGe
Eligibility criteria from pharmaceutical randomised controlled trials of idiopathic pulmonary fibrosis: a registry-based study
Authors: Yet H. Khor, Max Schulte, Kerri A. Johannson, Veronica Marcoux, Jolene H. Fisher, Deborah Assayag, Helene Manganas, Nasreen Khalil, Martin Kolb, Christopher J. Ryerson, Gerard Cox, Charlene D. Fell, Andrea S. Gershon, Nicole Goh, Andrew J. Halayko, Stacey Lok, Julie Morisset, Mohsen Sadatsafavi, Shane Shapera, Teresa To, Pearce G. Wilcox, Alyson W. Wong
Journal: European Respiratory Journal (2023)

Background Little is known about generalisability of randomised controlled trials (RCTs) for idiopathic pulmonary fibrosis (IPF). We evaluated eligibility criteria for phase III IPF RCTs to determine their representativeness in clinical registries, and calculated forced vital capacity (FVC) changes according to eligibility criteria. Methods Common eligibility criteria used in &gt;60% of IPF RCTs were identified from a literature search and applied to patients with IPF from prospective Australian and Canadian registries. Additional pre-specified criteria of 6-min walk distance (6MWD) and different measures of preceding disease progression were also evaluated. Joint longitudinal-survival modelling was used to compare FVC decline according to eligibility for individual and composite criteria. Results Out of 990 patients with IPF, 527 (53%) met all common RCT eligibility criteria at the first clinic visit, including 343 with definite IPF and 184 with radiological probable usual interstitial pneumonia pattern without histological confirmation ( i.e. provisional IPF). The percentages of eligible patients for landmark RCTs of nintedanib and pirfenidone were 19–50%. Adding 6MWD ≥150 m and different measures of preceding disease progression to the composite common criteria reduced the percentages of patients meeting eligibility to 52% (n=516) and 4–18% (n=12–61), respectively. Patients meeting the composite common criteria had less-rapid 1-year FVC decline than those who did not (−90 versus −103 mL, p=0.01). Definite IPF generally had more-rapid 1-year FVC decline compared to provisional IPF. Conclusions Eligibility criteria of previous IPF RCTs have limited generalisability to clinical IPF populations, with FVC decline differing between eligible and ineligible populations.
Possible Undetected Mpox Infection Among Persons Accessing Homeless Services and Staying in Encampments — San Francisco, California, October–November 2022
Authors: Caroline J. Waddell, Thomas D. Filardo, Namrata Prasad, Gerald J. Pellegrini, Neela Persad, William C. Carson, Terese Navarra, Michael B. Townsend, Panayampalli S. Satheshkumar, David Lowe, Deborah Borne, Julia Janssen, Nnenna Okoye, Anamaría Bejarano, Grace E. Marx, Emily Mosites
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Monkeypox (mpox) is a disease caused by an Orthopoxvirus. The 2022 multinational outbreak, which began in May 2022, has spread primarily by close skin-to-skin contact, including through sexual contact. Persons experiencing homelessness have been disproportionately affected by severe mpox (1). However, mpox prevalence and transmission pathways among persons experiencing homelessness are not known, and persons experiencing homelessness have not been specifically recommended to receive mpox vaccine during the 2022 outbreak (2,3). During October 25-November 3, 2022, a CDC field team conducted an orthopoxvirus seroprevalence survey among persons accessing homeless services or staying in encampments, shelters, or permanent supportive housing in San Francisco, California that had noted at least one case of mpox or served populations at risk. During field team visits to 16 unique sites, 209 participants completed a 15-minute survey and provided a blood specimen. Among 80 participants aged <50 years who did not report smallpox or mpox vaccination or previous mpox infection, two (2.5%) had detectable antiorthopoxvirus immunoglobulin (Ig) G antibody. Among 73 participants who did not report mpox vaccination or previous mpox infection and who were tested for IgM, one (1.4%) had detectable antiorthopoxvirus IgM. Together, these results suggest that three possible undetected mpox infections occurred among a sample of persons experiencing homelessness, highlighting the need to ensure that community outreach and prevention interventions, such as vaccination, are accessible to this population.
Comprehensive Metabolic Tracing Reveals the Origin and Catabolism of Cysteine in Mammalian Tissues and Tumors
Authors: Sang Jun Yoon, Joseph A. Combs, Aimee Falzone, Nicolas Prieto-Farigua, Samantha Caldwell, Hayley D. Ackerman, Elsa R. Flores, Gina M. DeNicola
Journal: Cancer Research (2023)

Abstract Cysteine plays critical roles in cellular biosynthesis, enzyme catalysis, and redox metabolism. The intracellular cysteine pool can be sustained by cystine uptake or de novo synthesis from serine and homocysteine. Demand for cysteine is increased during tumorigenesis for generating glutathione to deal with oxidative stress. While cultured cells have been shown to be highly dependent on exogenous cystine for proliferation and survival, how diverse tissues obtain and use cysteine in vivo has not been characterized. We comprehensively interrogated cysteine metabolism in normal murine tissues and cancers that arise from them using stable isotope 13C1-serine and 13C6-cystine tracing. De novo cysteine synthesis was highest in normal liver and pancreas and absent in lung tissue, while cysteine synthesis was either inactive or downregulated during tumorigenesis. In contrast, cystine uptake and metabolism to downstream metabolites was a universal feature of normal tissues and tumors. However, differences in glutathione labeling from cysteine were evident across tumor types. Thus, cystine is a major contributor to the cysteine pool in tumors, and glutathione metabolism is differentially active across tumor types. Significance: Stable isotope 13C1-serine and 13C6-cystine tracing characterizes cysteine metabolism in normal murine tissues and its rewiring in tumors using genetically engineered mouse models of liver, pancreas, and lung cancers.
Change of Article Status to Open Access
Authors: Tao Yuan, Qin Ma, Ming-Ming Zhang, Pan Chi
Journal: JAMA Oncology (2023)

Anthony E. Mascia, PhD; Emily C. Daugherty, MD; Yongbin Zhang, MS; Eunsin Lee, PhD; Zhiyan Xiao, PhD; Mathieu Sertorio, PhD; Jennifer Woo, BSc; Lori R. Backus, BA; Julie M. McDonald, CCRP; Claire McCann, PhD; Kenneth Russell, MD; Lisa Levine, PhD; Ricky A. Sharma, MD, PhD; Dee Khuntia, MD; Jeffrey D. Bradley, MD; Charles B. Simone II, MD; John P. Perentesis, MD; John C. Breneman, MD